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    An immunohistochemical study on the evaluation of mast cell, interleukin 17 and interleukin 1β profile in contagious caprine pleuropneumonia
    (Urmia Univ, 2024) Karatas, Ozhan; Akcakavak, Gokhan
    Contagious caprine pleuropneumonia (CCPP) in goats is defined as a highly contagious and rapidly spreading mycoplasmal disease that is now among the leading causes of major economic losses on many continents (Asia, Africa and the Middle East). In this study, we aimed to evaluate immunohistochemically mast cells (MCs) profile and local interleukin (IL)-17 and IL-1(3 protein expressions in naturally infected CCPP according to the course of the inflammation (peracute-acute, subacute-chronic). The material of the study consisted of 40 naturally infected CCPP and 6 healthy control goat lung tissues. Appropriate samples were taken from the necropsied goats and subjected to histopathological and immunohistochemical examination. In the histopathological examination of the samples, it was determined that 29 samples had a peracute-acute course and 11 had a subacute-chronic course. In immunohistochemical examination, MC profile and local IL-17 and IL-1(3 protein expressions were evaluated in the peracute-acute and subacute-chronic course. Immunohistochemically, significant increases in MC number, local IL-17 and IL-1(3 scores were detected in the peracuteacute course compared to the control group. There were significant decreases in the relevant scores in the subacute-chronic course compared to the peracute-acute course. Current findings indicated that MC, IL-17, and IL-1(3 expressions played important roles in the pathogenesis of infection in naturally infected CCPP, especially in the peracute-acute course. Additionally, MC profile was evaluated for the first time in naturally infected CCPP. (c) 2024 Urmia University. All rights reserved.
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    Determination by Immunohistochemistry of Acute Phase Proteins in Naturally Infected Sheep with Listeriosis
    (Sciendo, 2025) Karatas, Ozhan; Akcakavak, Gokhan
    Listeriosis is an infectious and fatal disease affecting domestic mammals, poultry, and humans worldwide. The effectiveness of local tissue expression of acute phase proteins in listeriosis in domestic mammals is not yet clear. The aim of this study is to evaluate the local expression of acute phase proteins in 26 brainstem tissue samples according to the distribution and severity of inflammation due to natural Listeriosis disease in sheep. The study material consisted of 26 brainstem paraffin blocks, including 20 from listeriosis-infected cases and 6 from healthy controls. Sections obtained from the paraffin blocks were subjected to histopathological and immunohistochemical analyses. Histopathological examination revealed normal histological structures in the brainstems of the control group. In contrast, brainstem sections from listeriosis cases exhibited histopathological findings such as micro abscesses composed of neutrophil granulocytes and microglial cells, gliosis, meningitis, congestion, perivascular cuffs, neuronal degeneration, and neuronophagia. Based on the distribution and severity of inflammation, listeriosis cases were categorized into three groups: 5 mild cases (Group I), 8 moderate cases (Group II), and 7 severe cases (Group III). Immunohistochemical analysis demonstrated significantly increased expression levels of C-reactive protein (CRP), Haptoglobin (Hp), and Serum Amyloid A (SAA) in listeriosis groups compared to the control group, with the highest statistical scores observed in Group II and Group III (p<0.001). The findings of this study suggest that acute-phase proteins may play crucial roles in the pathophysiological processes of naturally infected listeriosis and could express locally. Particularly, the increased expression of these proteins with the progression of inflammation may provide valuable insights into disease severity and the infection process.
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    Determination of Apoptosis, Necroptosis and Autophagy Markers by Real-time PCR in Naturally Infected Pneumonic Pasteurellosis caused by Pasteurella multocida and Mannheimia haemolytica in Cattle
    (Univ Agriculture, Fac Veterinary Science, 2024) Akcakavak, Gokhan; Karatas, Ozhan; Tuzcu, Nevin; Tuzcu, Mehmet
    Pneumonic pasteurellosis (PP) is defined as one of the pivotal infectious diseases caused by Pasteurella multocida and Mannheimia haemolytica . This study aimed to determine the levels of Bcl-2-associated protein X (Bax), B-cell lymphoma 2 (Bcl2), caspase-3, autophagy related-5 (Atg5), beclin-1 and receptor interacting protein3 ( RIP3) in lung tissues with naturally infected PP caused by P. multocida and M. haemolytica , and to reveal their effects on the pathogenesis of P. multocida and M. haemolytica pneumonia. The material of the study consisted of 150 fibrinous pneumonia/pleuropneumonia and 10 healthy lung tissue samples. Relevant samples were examined by histopathological, immunohistochemical and real-time PCR methods. Immunohistochemically, 23 (15.3%) were positive for P. multocida, and 17 (11.3%) were positive for M. haemolytica . Subsequently, the processes of apoptosis, autophagy and necroptosis for P. multocida and M. haemolytica were evaluated by real-time PCR. P. multocida pneumonia increased Bax, Caspase-3, Atg5, Beclin-1, and RIP3 gene expressions (4.2, 3.8, 2.9, 2.1, 2.8-fold, respectively), whereas Bcl-2 gene expression was decreased (0.22-fold). While Bax, Caspase-3, Atg5, Beclin-1, and RIP3 gene expressions were increased in M. haemolytica pneumonia (2.3, 1.9, 1.7, 1.2, 4.2-fold, respectively), it was observed that Bcl-2 gene expression was reduced (0.52-fold). The results obtained in the study revealed the importance of necroptosis, apoptosis and autophagy processes in the pathogenesis of PP caused by P. multocida and M. haemolytica and contributed to the literature. In addition, we found that the processes of apoptosis and autophagy play a more active role in PP caused by P. multocida , and the process of necroptosis plays a more active role in PP caused by M. haemolytica.
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    Eucalyptol regulates Nrf2 and NF-kB signaling and alleviates gentamicin-induced kidney injury in rats by downregulating oxidative stress, oxidative DNA damage, inflammation, and apoptosis
    (Taylor & Francis Ltd, 2024) Akcakavak, Gokhan; Kazak, Filiz; Karatas, Ozhan; Alakus, Halil; Alakus, Ibrahim; Kirgiz, Omer; Celik, Zeynep
    Gentamicin, an aminoglycoside antibiotic, is nowadays widely used in the treatment of gram-negative microorganisms. The antimicrobial, anti-inflammatory, and antioxidant activities of eucalyptol, a type of saturated monoterpene, have been reported in many studies. The aim of this study was to examine the possible effects of eucalyptol on gentamicin-induced renal toxicity. A total of 32 rats were divided into 4 groups; Control (C), Eucalyptol (EUC), Gentamicin (GEN), and Gentamicin + Eucalyptol (GEN + EUC). In order to induce renal toxicity, 100 mg/kg gentamicin was administered intraperitoneally (i.p.) for 10 consecutive days in the GEN and GEN + EUC groups. EUC and GEN + EUC groups were given 100 mg/kg orally of eucalyptol for 10 consecutive days. Afterwards, rats were euthanized and samples were taken and subjected to histopathological, biochemical, immunohistochemical, and real-time PCR examinations. The blood urea nitrogen (BUN) and creatinine (CRE) levels were significantly decreased in the GEN + EUC group (0.76 and 0.69-fold, respectively) compared to the GEN group. The glutathione peroxidase (GPx) and catalase (CAT) activities were significantly increased in the GEN + EUC group (1.35 and 2.67-fold, respectively) compared to the GEN group. In GEN group, Nuclear factor kappa B (NF-kB), Interleukin 1-beta (IL-1 beta), Inducible nitric oxide synthase (iNOS), Tumor necrosis factor-alpha (TNF-alpha), Caspase-3, 8-Hydroxy-2 '-deoxyguanosine (8-OHdG) and Nuclear factor erythroid 2-related factor (Nrf2) expression levels were found to be quite irregular. GEN + EUC group decreased the expressions of NF-kB, IL-1 beta, iNOS, TNF-alpha, Caspase-3, and 8-OHdG (0.55, 0.67, 0.54, 0.54, 0.63 and 0.67 fold, respectively), while it caused increased expression of Nrf2 (3.1 fold). In addition, eucalyptol treatment ameliorated the histopathological changes that occurred with gentamicin. The results of our study show that eucalyptol has anti-inflammatory, antioxidative, antiapoptotic, nephroprotective, and curative effects on gentamicin-induced nephrotoxicity.
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    Evaluation of local expressions of acute phase proteins in white muscle disease in lambs by the immunohistochemical method
    (Universidad del Zulia, Facultad de Ciencias Veterinarias, 2024) Karatas, Ozhan; Akcakavak, Gokhan
    White muscle disease (WMD) and/or nutritional muscular dystrophy is defined as a disease with a generally acute course that results in degeneration and necrosis of the heart muscle. In this study, it was aimed to reveal local tissue expressions of acute phase proteins such as C–reactive protein (CRP), Serum amyloid–A (SAA) and Haptoglobin (Hp) in lambs with WMD. The study material consisted of 27, one–six months old lamb heart tissues, 6 of which were healthy and 21 with WMD. The lambs were necropsied, and the relevant heart samples were taken into neutral formaldehyde. Afterwards, paraffin blocks were obtained by going through routine tissue follow–up processes. Sections were taken from paraffin blocks and stained with Hematoxylin–Eosin (H–E) and Immunohistochemical methods. Histopathologically, control groups exhibited normal histology. Hyaline degeneration, Zenker necrosis, calcification, inflammatory cell infiltration and an increase in connective tissue were detected in the heart tissues of lambs with WMD. Lambs with WMD had significantly increased CRP and SAA proteins compared to control (P<0.01). However, there was no difference between the groups in Hp (P>0.05). In conclusion, local tissue expressions of CRP, SAA and Hp in lambs with WMD were identified immunohistochemically for the first time. It is possible to say that CRP and SAA may play important roles in the pathophysiology of WMD and that CRP and SAA may provide more sensitive results in the diagnosis and prognosis of the disease. © (2023), (Universidad del Zulia). All Rights Reserved.
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    Proanthocyanidin alleviates testicular torsion/detorsion-induced ischemia/ reperfusion injury in rats
    (Churchill Livingstone, 2024) Kazak, Filiz; Akcakavak, Gokhan; Alakus, Ibrahim; Alakus, Halil; Kirgiz, Omer; Karatas, Ozhan; Deveci, Mehmet Zeki Yilmaz
    Testicular torsion is an urological emergency and can lead to ischemia damage and testicular loss if not diagnosed in time. Proanthocyanidin is reported to have anti-inflammatory and antioxidant properties. The current study aimed to examine the possible effects of proanthocyanidin (P) on the testis in torsion/detorsion (T/D)induced testicular ischemia/reperfusion (I/R) injury in rats. Forty rats were divided into four groups (n=10 for each): sham-operated (sham), I/R, I/R + P100 (100 mg/kg, 30 min before torsion), and I/R + P200 (200 mg/kg, 30 min before torsion). Testicular T/D was performed on the left testicle by 3 hours of torsion at 720 degrees clockwise, followed by 3 hours of detorsion. In the I/R group, an increase in malondialdehyde (MDA) levels and a decrease in glutathione (GSH), vitamin C (Vit C), glutathione peroxidase (GPx), glucose-6-phosphate dehydrogenase (G6PD) values were determined compared to the sham group (p <0.001). Moreover, an increase in the expression of cleaved caspase-3 and Bcl2-associated X protein (Bax), a decrease in the expression of B-cell lymphoma 2 (Bcl2) and proliferating cell nuclear antigen (PCNA) were detected in the I/R group (p <0.001). Histopathologically, it was determined that the Johnsen and Cosentino scores of the testicles were irregular in the I/R group (p <0.001). Proanthocyanidin treatment caused a decrease in MDA, cleaved caspase-3 and Bax levels and an increase in GSH, Vit C, GPx, G6PD, Bcl-2 and PCNA values. Additionally, Johnsen and Cosentino rearranged the scores. The present findings revealed the protective and curative effects of proanthocyanidin in organ damage due to testicular torsion/detorsion-induced ischemia/reperfusion with their antioxidative and antiapoptotic properties.
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    Tarantula cubensis alcohol extract enhances the tumoricidal effect of capecitabine via multiple pathways in azoxymethane-induced colorectal cancer in rats
    (University of Benin, 2024) Akcakavak, Gokhan; Celik, Zeynep; Karatas, Ozhan; Dogan, Osman; Ozdemir, Ozgur; Tuzcu, Mehmet
    Purpose: To evaluate the effect of a combination of Tarantula cubensis alcohol extract (TCAE) and capecitabine (CAP) in the treatment of azoxymethane (AOM)-induced colorectal cancer (CRC). Methods: Forty-two Wistar albino rats were divided into 7 groups with 6 rats in each group. The groups consisted of Control (C), Control+TCAE (C-TCAE), Control+CAP (C-CAP), Cancer control (CC), Cancer+TCAE (CC-TCAE), Cancer+CAP (CC-CAP) and Cancer+CAP+TCAE (CC-CAP+TCAE). To induce CRC, AOM (15 mg/kg) was administered to rats subcutaneously (sc) twice at a one-week interval to all the groups except control. From the 15th week, TCAE (0.2 mL/rat sc) was administered to CC-TCAE group every 3 days for 4 weeks, and CAP (40 mg/kg/day) was administered by gavage to CC-CAP group for 4 weeks. In CC-CAP+TCAE group, TCAE (0.2 mL/rat sc) was administered every 3 days for 4 weeks, and CAP (40 mg/kg/day) was administered gavage for 4 weeks. Animals were treated for 18 weeks. Aberrant crypt foci (ACF) were evaluated histopathologically among CC, CC-TCAE, CC-CAP, and CC-CAP+TCAE groups. ?-catenin, CD15, Proliferating Cell Nuclear Antigen (PCNA), and Nuclear Factor kappa B (NF-?B) expression levels were immunohistochemically compared among all groups. Results: Histopathologically, ACF scores were significantly increased in CC group, while a significant decrease in the relevant scores (p < 0.001) was observed in CC-CAP and CC-CAP+TCAE treatment groups, and the lowest scores were in CC-CAP+TCAE group. Immunohistochemically, in CC group, ?-catenin, Nuclear Factor kappa B (NF-?B), Proliferating Cell Nuclear Antigen (PCNA) and CD15 expressions were highly irregular. CC-CAP and CC-CAP+TCAE groups had significantly reduced expressions (p < 0.001), and the lowest expressions were in CC-CAP+TCAE group. Conclusion: The combined use of TCAE and CAP in treatment of CRC has a synergistic effect and increases the anticancer efficacy of TCAE, and CAP. More studies at the molecular level are needed in the future to demonstrate the clinical benefit of TCAE supplementation during the treatment of CRC with CAP. © 2024 The authors. This work is licensed under the Creative Commons Attribution 4.0 International License.